This is a resubmission of an application for a mentored patient-oriented K-23 award, designed to enhance clinical training and research expertise in the area of major depression and the role of nutrition in the development and treatment of depressive disorders. This proposal differs from the original in that it uses an omega-3 mix as opposed to pure DHA; consists of a double blind omega-3 versus placebo acute treatment phase, followed by a continuation phase of open treatment for non-responders, and continued treatment for responders with the double blind medication from the acute phase; and includes more modern biostatistical techniques. Omega-3 long chain fatty acids are found in eggs, red meats, and cold-water fish. There is one recently published small clinical trial with bipolar patients and a few case reports/series with psychotic patients, suggesting that omega-3 fatty acid mixes may have a role in symptom alleviation in depression, bipolar disorder, and psychotic disorders. Research on omega-3s as well as other natural treatments represents an underdeveloped area in psychopharmacology, and rigorous studies in this field are needed. The goals of the project will be to assess the role of omega-3 fatty acid mix compared to placebo in the treatment of major depression. Additional studies will examine the nutritional status of depressed patients vis-a-vis intake of fish and other omega-3-rich foods. The proposed study will be based at the Massachusetts General Hospital in the Depression Clinical and Research Program, under the mentorship of Maurizio Fava, MD, and will include consultation from experts. There will also be a didactic component to the project, including coursework in biostatistics and research design, nutrition science, and ethics. The development of a larger scale RO1 project comparing omega-3 fatty acids to a selective serotonin reuptake inhibitor (SSRI) for treatment of depression will be started during the last two years of the project period. It is hoped that this project will provide the critical fund of basic knowledge and practical experience necessary to aid the candidate in becoming an independent investigator.